1. Field of the Invention
The present invention relates generally to the preparation of desflurane (CF3CFHOCF2H), which is a well known inhalation anesthetic.
2. Description of Related Art
There are several known processes to manufacture desflurane in which the desired product is obtained mixed with hydrogen fluoride, where the hydrogen fluoride can either be a reagent or can be generated as a byproduct. In all cases the hydrogen fluoride is removed from the desflurane by washing with water. It is known to those skilled in the art that it is very difficult to separate hydrogen fluoride from water, which makes the process both economically and environmentally unfavorable.
One method to prepare desflurane (U.S. Pat. No. 6,054,626) involves the reaction of 2-difluoromethoxy-1,1,1-trifluoroethane (CF3CH2OCF2H) with a transition metal fluoride fluorinating agent, where the fluorinating agent is cobalt trifluoride (CoF3). The reaction forms hydrogen fluoride as a by-product. The process according to the examples removes the hydrogen fluoride by-product by washing the crude reaction mixture with water.
Desflurane can also be prepared by the reaction of isoflurane (CF3CClHCF2H) with excess hydrogen fluoride in the presence of antimony pentachloride, alone or in combination with antimony trichloride (U.S. Pat. Nos. 5,026,924 and 6,800,786). This process removes the highly toxic antimony salts as an aqueous stream along with the hydrogen fluoride by washing the crude reaction mixture with water.
Recently, we have disclosed an invention where we prepared desflurane by reaction of isoflurane and excess hydrogen fluoride over a chromia catalyst (U.S. Provisional Application No. 60/643,301, filed on Jan. 12, 2005, the entire contents of which are hereby incorporated by reference).
There remains a need in the art to discover ways to separate/purify desflurane from crude reaction mixtures comprising hydrogen fluoride, and especially to avoid the need to remove hydrogen fluoride by washing with water.